天然黄酮类化合物在治疗阿尔茨海默病中的β-位点 APP 分解酶-1 抑制作用

Sandeep Singh, Virendra Kushwaha, Shriram Sisodia, Shivendra Kumar, Kantrol Kumar Sahu
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摘要

阿尔茨海默病(AD)是一种破坏性神经系统疾病,其特征是认知功能逐渐衰退,包括记忆力减退、推理困难和迷失方向。其特征包括在大脑中形成神经纤维缠结和神经斑块,从而破坏神经元的正常功能。由磷酸化 tau 蛋白组成的神经纤维缠结和含有淀粉样-β 蛋白(Aβ)聚集体的神经斑块是导致退化过程的原因。1999 年,β 位淀粉样前体蛋白裂解酶 1(BACE1)的发现彻底改变了我们对注意力缺失症发病机制的认识。BACE1 在产生 Aβ(一种与注意力缺失症进展有关的毒性蛋白)的过程中发挥着至关重要的作用。据观察,AD 大脑和体液中的 BACE1 水平升高,凸显了它在疾病发生和发展过程中的重要作用。尽管 BACE1 抑制剂的临床试验因疗效和安全性问题而受挫,但针对 BACE1 的治疗仍是一种很有前景的早期 AD 治疗策略。天然类黄酮已成为潜在的 BACE1 抑制剂,它能减少神经细胞中 Aβ 的产生并抑制 BACE1 的活性。在综述中,我们深入探讨了 AD 的病理生理学,强调了 BACE1 在 Aβ 生成和疾病进展中的核心作用。我们探讨了 BACE1 抑制剂(包括天然类黄酮)在控制 AD 症状方面的治疗潜力。此外,我们还深入探讨了该领域正在进行的临床试验和现有专利,为未来的 AD 治疗研究指明了方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Beta-Site APP-Cleaving Enzyme-1 Inhibitory Role of Natural Flavonoids in the Treatment of Alzheimer's Disease.

Alzheimer's Disease (AD) is a devastating neurological condition characterized by a progressive decline in cognitive function, including memory loss, reasoning difficulties, and disorientation. Its hallmark features include the formation of neurofibrillary tangles and neuritic plaques in the brain, disrupting normal neuronal function. Neurofibrillary tangles, composed of phosphorylated tau protein and neuritic plaques, containing amyloid-β protein (Aβ) aggregates, contribute to the degenerative process. The discovery of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) in 1999 revolutionized our understanding of AD pathogenesis. BACE1 plays a crucial role in the production of Aβ, the toxic protein implicated in AD progression. Elevated levels of BACE1 have been observed in AD brains and bodily fluids, underscoring its significance in disease onset and progression. Despite setbacks in clinical trials of BACE1 inhibitors due to efficacy and safety concerns, targeting BACE1 remains a promising therapeutic strategy for early-stage AD. Natural flavonoids have emerged as potential BACE1 inhibitors, demonstrating the ability to reduce Aβ production in neuronal cells and inhibit BACE1 activity. In our review, we delve into the pathophysiology of AD, highlighting the central role of BACE1 in Aβ production and disease progression. We explore the therapeutic potential of BACE1 inhibitors, including natural flavonoids, in controlling AD symptoms. Additionally, we provide insights into ongoing clinical trials and available patents in this field, shedding light on future directions for AD treatment research.

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